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To compare the short-term effects of inhaled nitric oxide (NO) and prone positioning in improving oxygenation in acute respiratory distress syndrome (ARDS).Charts of consecutive ARDS patients (lung injury score >2) during a 2-yr period, tested for both inhaled NO and prone positioning efficacy were retrospectively reviewed. Variations in the PaO2/FIO2 ratio induced by inhaled NO and prone positioning were evaluated.Twenty-seven patients (age, 42 ± 17 yrs) were included. Simplified Acute Physiology Score II was 45 ± 14. Mortality rate in the intensive care unit was 63%. The causes of ARDS were pneumonia (n = 14), extra-lung infection (n = 5), and noninfectious systemic inflammatory response syndrome (n = 8). Lung injury score was 2.7 ± 0.3. At baseline, before the initiation of inhaled NO, the PaO2/FIO2 ratio was 97 ± 46 torr and before prone positioning, 92 ± 26 torr. Variations in the PaO2/FIO2 ratio were lower at start of NO therapy (11 ± 4 ppm) than that observed at prone positioning initiation (23 ± 31 vs. 62 ± 78 torr, p < .05). An increase in variations in the PaO2/FIO2 ratio of > 15 torr was associated with prone positioning in 16 patients (59%) and with NO inhalation in 13 patients (48%) (not significant). An increase in variations in the PaO2/FIO2 ratio of > 15 torr was associated with both techniques in only six patients (22%). There was no correlation between the response to prone positioning and the response to inhaled NO (r2 = .005;p= .73).Prone positioning improves hypoxemia significantly better than does inhaled NO. The response to one technique is not predictive of the response to the other technique.